In the field of chromatography, such as high performance liquid chromatography (HPLC), gas chromatography (GC), supercritical fluid chromatography (SFC), and capillary electrochromatography (CEC), a cartridge is often installed in-line with a chromatography column. If the cartridge packing consists of the same material as the column packing, it is called a guard cartridge and protects the column from contamination. If the cartridge contains filtration material, the cartridge is a filter and functions to remove particulates from the mobile phase. The cartridge may also work as a sample concentrator, or as a solid phase derivatization device based on the properties of the cartridge packing. The cartridge may be constructed to have the shape of column, disk, or tubule. For installation of the cartridge in-line to a chromatography column, a cartridge holder is required. It is well established that dead volume in the connection between a tubing and a column inlet significantly affects the performance of the column. For example, the dead volume causes poor separation and peak broadening and overlap, and makes it very difficult to identify and quantify species in the sample, if not impossible. Those problems are even more serious when a small quantity of samples is involved. Although efforts have been made to minimize the dead volume by designing connection unions of different structures, it is not a easy job for an ordinary user to make a connection with minimal dead volume and great caution has to be taken during a connecting operation.
A conventional cartridge holder typically consists of three parts: inlet fitting 110, holder body 120, and outlet fitting 130 as depicted in FIG. 1. In this holder each end of tube 160 is separately connected to either column 180 or fitting 130. Cartridge 150 is secured in holder body 120 by fittings 110 and 130. Cartridge holder 100 is in-line connected to endfitting 170 of chromatography column 180 through tube 160 by finger tights 140. Since HPLC requires connections with minimal dead volume one must screw finger tight 140 and simultaneously press tube 160 against fitting 130 or 170 to ensure that the tube end is in close contact with the fitting. Obviously, this is an inconvenient process and runs the risk of generating dead volume during the connection. Another disadvantage is that, using two finger tights 140 for the connection between cartridge holder 100 and column 180, results in a long flow path for mobile phases, degrading column performance. Moreover, the two finger tights 140 have to be tightened separately and more time is needed to complete the connection.
Other cartridge holders include a two-piece cartridge holder of FIG. 2. The cartridge holder 200 has an end cap 210 and holder body 220. At the outlet side of the holder body 220, a threaded male coupling 221 with thin hole 222 extends out. Cartridge 250 is secured in body 220 by threading end cap 210 into holder body 220. To connect cartridge holder 200 onto chromatography column 280, the male coupling 221 of holder body 220 is screwed into endfitting 270 of column 280. Tapered section 223 is pressed against ferrule seat 271 of endfitting 270 to seal the connection. The pilot depth 272 of endfitting 270 is filled by pilot extension 224 of holder body 220 to reduce the dead volume of the connection. The two-piece cartridge holder can be directly screwed onto a chromatography column and that simplifies the connection process.
But the two-piece cartridge holder 200 has limitations. One major limitation is the compatibility of the holder connection. Many brands of column endfittings exist and each has a different configuration. Even if female thread 273 and ferrule seat 271 of endfitting 270 of column 280 are standardized, significant variation in the length of pilot depth 272 exists. If the length of pilot depth 272 of endfitting 270 is longer than the length of pilot extension 224 of cartridge holder 200, dead volume will be produced once cartridge holder 200 is screwed onto endfitting 270. If the length of pilot depth 272 of endfitting 270 is shorter than the length of pilot extension 224 of cartridge holder 200, tapered section 223 cannot be pressed tightly against ferrule seat 271, causing the connection to leak. This means that the two-piece cartridge holder 200 of defined pilot extension 224 can only be connected onto a column with the endfitting 270 of matched pilot depth 272. Moreover, most column users are not aware of the brand of the endfitting for the column they are using and often find it difficult to choose a suitable cartridge holder for the column. Further, small dimensional differences can exist that are not detectable visually, but which can greatly degrade performance.
Another cartridge is described in FIG. 3, in which the cartridge consists of two pieces. Inner piece 340 contains cartridge 341, tube 342, ferrule seat 343, and pilot depth 344. Outer piece 320 consists of female thread 321, cavity 322, channel 323, male thread 324, and tapered section 325. Inner piece 340 can move longitudinally in cavity 322 and channel 323.
For connection, cartridge holder 300 is screwed into endfitting 370 of column 380 and tightened to the extent that tapered section 325 of outer piece 320 is in contact with ferrule seat 371, but is not tight enough to grip and hold tubing 342 so that tubing 342 is still movable. The correct tightness is very difficult to achieve. A standard nut 310 with tubing 311 is then screwed into cavity 322 in cartridge holder 300 through female thread 321 and pushes inner piece 340 forward until the end of tube 342 of inner piece 340 reaches the bottom of pilot depth 372 of endfitting 370. A minimal dead-volume connection is supposed to be achieved in this way. Cartridge 300 is then firmly tightened to seal the connection with endfitting 370.
Though this design of FIG. 3 is supposed to match most column endfittings, it is not easy to determine how much tightening should be made in each step. For example, if cartridge 300 is tightened firmly to endfitting 370 before nut 310 screws in, then tube 342 of inner piece 340 will not move when nut 310 is threading in cartridge holder 300 and the end of tube 342 may be unable to move forward to fill pilot depth 372, thus increasing the dead volume. Further, tube 342 has a nonsupported portion 342a in cavity 322 of outer piece 320 to allow an adjustable range. Since sealing pressure from nut 310 is transferred entirely onto tube 342, a high sealing force is not acceptable for this design due to the possibility of breakage or deformation of the nonsupported portion 342a. Currently the design is believed only suitable for a miniaturized cartridge format.
When connecting a tubing to a chromatography column, similar problems as discussed above exist. In particular, it is difficult to achieve zero dead volume using conventional connecting union.
A cartridge holder with application multiplicity, column-fitting compatibility, and operation simplicity is needed.